Development and characterization of polysiloxane-based gel loaded with phytoingredients encapsulated in phytosomes for scar management.

Recent research has emphasized the development of efficient drug delivery systems to facilitate the delivery of biological compounds such as polyphenols via skin absorption. Phytozomes have been employed as carriers of plant compounds in this context Hydrogen bonding between plant polyphenols and the phospholipid phosphate group enables efficient encapsulation of potent compounds for enhanced drug delivery systems. Additionally, the strong affinity of phytosomes for the skin's phospholipids enhances skin absorption. In this study, phytosomes were initially formulated using the thin-layer hydration method After optimizing the synthetic parameters, phytosomes were loaded with Resveratrol and Quercetin for enhanced delivery and skin absorption potential to assess the characteristics of the synthesized phytosomes, tests were conducted to determine particle distribution and size, zeta potential, and examine the microstructure morphology using a scanning electron microscope (SEM). Furthermore, a siloxane gel base was formulated in this study, and the stability of the physicochemical and biological properties of the final prepared nanoformulation was investigated. The results of this study indicated that the formulated phytosomes exhibit optimal characteristics for facilitating high skin penetration of resveratrol and quercetin. A high skin absorption was observed after 60 days of synthesis. Additionally, the base of the siloxane gel can play a significant role in preventing the formation of scars by reducing the passage of water vapor.

Hyaluronic Acid-Modified Micelles of Azithromycin and Quercetin Against Infections Caused by Methicillin-Resistant Staphylococcus Aureus.

Introduction: Resistance of intracellular pathogens is a challenge in microbial therapy. Methicillin-resistant Staphylococcus aureus (MRSA), which is able to persist inside the cells of infected tissues, is protected from attack by the immune system and many antimicrobial agents. To overcome these limitations, nano-delivery systems can be used for targeted therapy of intracellular MRSA. Methods: Hyaluronic acid-modified azithromycin/quercetin micelles (HA-AZI/Qe-M) were synthesized by thin film hydration. The micelles were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and Fourier transform infrared spectroscopy (FTIR), and the drug loading (DL) and encapsulation efficiency (EE) were detected by high performance liquid chromatography (HPLC). The uptake ability of RAW264.7 cells was investigated, and its distribution in mice was evaluated by in vivo imaging. The inhibitory effect of the micelles against MRSA in vitro and its ability to eliminate intracellular bacteria were evaluated. Bacterial muscle-infected mice were constructed to evaluate the therapeutic effect of the micelles on bacterial infections in vivo and the biocompatibility of the micelles was investigated. Results: HA-AZI/Qe-M had suitable physical and chemical properties and characterization. In vitro antibacterial experiments showed that HA-AZI/Qe-M could effectively inhibit the growth of MRSA, inhibit and eliminate the biofilm formed by MRSA, and have an excellent therapeutic effect on intracellular bacterial infection. The results of RAW264.7 cells uptake and in vivo imaging showed that HA-AZI/Qe-M could increase the cellular uptake, target the infection site, and prolong the treatment time. The results of in vivo antibacterial infection experiments showed that HA-AZI/Qe-M was able to ameliorate the extent of thigh muscle infections in mice and reduce the expression of inflammatory factors. Conclusion: HA-AZI/Qe-M is a novel and effective nano-drug delivery system that can target intracellular bacterial infection, and it is expected to be safely used for the treatment of MRSA infection.

Synthesis and characterization of fullerene-based nanocarrier for targeted delivery of quercetin to the brain.

Aim: Preparation of quercetin fullerene conjugate (QFC) for nose-to-brain delivery and their in vitro and ex vivo characterizations.Methods: Carboxylated fullerene was converted into acetylated fullerene and quercetin was conjugated and physically adsorbed on acetylated fullerene.Results: The particle size and zeta potential of QFC and chitosan-coated QFC (CC-QFC) were found to be 179.2 ± 1.10, 293.4 ± 2.757, -5.28 ± 1.43 and 11.6 ± 0.4 respectively. The entrapment efficiency, loading efficiency of QFC were found to be 85.55% and 42.77%. The MTT assay revealed 80.69% SH-SY5Y cell viability at a concentration of 50 µg/ml. CC-QFC showed remarkable (89.20%) ex vivo mucoadhesive properties compared with QFC (66.67%). Further study showed no significant ciliotoxicity by CC-QFC.Conclusion: The obtained results suggested the potential of CC-QFC for treatment in Alzheimer's disease.

In our study, we developed a new method to deliver a natural substance called quercetin into the brain for the treatment of Alzheimer's disease. Quercetin is known for its health benefits, especially in protecting brain cells. We combined quercetin with a tiny carbon-based material called fullerene, which looks like a soccer ball, to create a new compound called quercetin fullerene conjugate (QFC). This QFC was designed to help quercetin reach the brain more effectively. To make it even better at reaching the brain, we coated QFC with a substance called chitosan. Coating it with chitosan can help to adhere it to nasal cavity for longer time for the delivery of quercetin to the brain. Importantly, our studies showed that this modified form of quercetin did not harm brain cells or the lining of the nose.Overall, our findings suggest that this new approach could be a promising way to develop treatments for Alzheimer's disease.

A one-stop integrated natural antimicrobial microneedles with anti-inflammatory, pro-angiogenic and long-term moisturizing properties to accelerate diabetic wound healing.

Diabetic ulcers present a formidable obstacle in diabetes management, typically leading to high mortality and amputation rates. To overcome traditional monotherapy drawbacks, We developed a novel microneedle strategy for combined antimicrobial action: ingeniously integrating quercetin with Platelet-derived Growth Factor-BB(PDGF-BB) and Sucrose Octasulfate(SOS) into the microneedle system(QPS MN). This method allows to penetrate through biofilms, administering quercetin nanocrystals and PDGF-BB deep into the tissue to combat microbial infection, mitigate inflammation, and promote angiogenesis. The accompanying backing material contains SOS, which absorbs wound exudate and forms a dressing that provides a moist environment for wound healing In an in vitro wound-scratch assay demonstrated that co-cultivating Human Umbilical Vein Endothelial Cells(HUVEC) with QPS MN for 48 h (90.3 ± 2.51 %) significantly enhanced cell migration compared to the control group (20.2 ± 1.41 %). Moreover, treatment of streptozotocin-induced diabetic wounds in rats with QPS MN for 14 days resulted in a wound healing rate of 96.56 ± 3.44 %, far surpassing the healing rate of only 40.34 ± 7.26 % observed in the untreated control group. Furthermore, the QPS MN treated wounds exhibited a notable increase in skin appendages and neovascularisation, indicating promising potential for achieving complete wound healing. These results suggest that QPS MN may offer substantial therapeutic benefits for addressing diabetic wounds.

Dietary Supplementation on Physical Performance and Recovery in Active-Duty Military Personnel: A Systematic Review of Randomized and Quasi-Experimental Controlled Trials.

BACKGROUND: Warfighters, often called tactical athletes, seek dietary supplementation to enhance training and recovery. Roughly 69% of active-duty US military personnel have reported consuming dietary supplements. The objective of this systematic review was to examine the impact of dietary supplements on muscle-related physical performance and recovery in active-duty military personnel. METHODS: Randomized controlled trials and quasi-experimental controlled trials of oral dietary supplementation in active-duty military members were examined. A protocol was registered (PROSPERO CRD42023401472), and a systematic search of MEDLINE and CINAHL was undertaken. Inclusion criteria consisted of studies published between 1990-2023 with outcomes of muscle performance and recovery among active-duty military populations. The risk of bias was assessed with the McMaster University Guidelines and Critical Review Form for Quantitative Studies. RESULTS: Sixteen studies were included. Four were conducted on protein or carbohydrate; four on beta-alanine alone, creatine alone, or in combination; two on mixed nutritional supplements; two on probiotics alone or in combination with beta hydroxy-beta methylbutyrate calcium; and four on phytonutrient extracts including oregano, beetroot juice, quercetin, and resveratrol. Ten examined outcomes related to physical performance, and six on outcomes of injury or recovery. Overall, protein, carbohydrate, beta-alanine, creatine, and beetroot juice modestly improved performance, while quercetin did not. Protein, carbohydrates, beta-alanine, probiotics, and oregano reduced markers of inflammation, while resveratrol did not. CONCLUSIONS: Nutrition supplementation may have small benefits on muscle performance and recovery in warfighters. However, there are significant limitations in interpretation due to the largely inconsistent evidence of ingredients and comparable outcomes. Thus, there is inadequate practical evidence to suggest how dietary supplementation may affect field performance.

Study on co-amorphous emerging solubilization behavior after gelation during dissolution: The importance of complexation and anti-crystallization.

Co-amorphous (CM) is a promising technology for enhancing the aqueous solubility of insoluble drugs, but the gelation phenomenon has often occurred during the dissolution process and seriously threatened their solubility/dissolution performance. Therefore, it's quite important to design favorable CM systems to alleviate or even avoid the adverse effects of gelation phenomenon. In this study, CM systems of taxifolin (TAX) and oxymatrine (OMT) (TAX-OMT CMs) were constructed to improve the solubility and dissolution properties of TAX. Interestingly, TAX-OMT CMs gradually aggregated and obviously gelled during dissolution, but the solubility and dissolution of TAX in TAX-OMT CMs were significantly enhanced compared to crystalline TAX. Consequently, the underlying solubilization mechanisms of TAX-OMT CMs after gelation were systematically explored. For one thing, the complexation between the two components in TAX-OMT CMs was verified by phase solubility, fluorescence spectroscopy and isothermal titration calorimetry. For another, the residual solids of TAX-OMT CMs after dissolution evaluation were thoroughly characterized by means of powder X-ray diffraction, fourier transform infrared spectroscopy, scanning electron microscopy, which showed the anti-crystallization property of TAX-OMT CMs. Furthermore, molecular simulation demonstrated the intermolecular interactions of TAX-OMT CMs alone and TAX-OMT complexes in aqueous solution. Finally, pharmacokinetics study in rats suggested that the bioavailability of TAX in TAX-OMT CM (1:2) was approximately 5.5-fold higher than that of crystalline TAX after oral administration. Collectively, this study reveals the importance of complexation and anti-crystallization effects of CM systems on maintaining solubilization behavior after gelation, providing an effective strategy to improve the absorption performance of pharmaceutical CM systems.

Highly functionalized pH-triggered supramolecular nanovalve for targeted cancer chemotherapy.

Chemotherapeutic drug delivery systems are commonly limited by their short half-lives, poor bioavailability, and unsuccessful targetability. Herein, pH-responsive hybrid NPs consist of benzimidazole-coated mesoporous silica nanoparticles (BZ-MSN) loaded with naturally occurring flavonoid quercetin (QUE-BZ-MSN). The NPs were further capped with beta-cyclodextrin (BCD) to obtain our desired BCD-QUE-BZMSN, with a zeta potential around 7.05 ± 2.37 mV and diameter about 115.2 ± 19.02 nm. The abundance of BZ onto the nanoparticles facilitates targeted quercetin chemotherapy against model lung and liver cancer cell lines. FTIR, EDX, and NMR analyses revealed evidence of possible surface functionalizations. Powder XRD analysis showed that our designed BCD-QUE-BZMSN formulation is amorphous in nature. The UV and SEM showed that our designed BCD-QUE-BZMSN has high drug entrapment efficiency and a nearly spherical morphology. In vitro, drug release assessments show controlled pH-dependent release profiles that could enhance the targeted chemotherapeutic response against mildly acidic regions in cancer cell lines. The obtained BCD-QUE-BZMSN nanovalve achieved significantly higher cytotoxic efficacy as compared to QUE alone, which was evaluated by in vitro cellular uptake against liver and lung cancer cell lines, and the cellular morphological ablation was further confirmed via inverted microscopy. The outcomes of the study imply that our designed BCD-QUE-BZMSN nanovalve is a potential carrier for cancer chemotherapeutics.

Quercetin ameliorates neuroinflammatory and neurodegenerative biomarkers in the brain and improves neurobehavioral parameters in a repeated intranasal amyloid-beta exposed model of Alzheimer's disease.

Objectives: The aim of the present study was to study the potential therapeutic effects of quercetin in protection against repeated intranasal exposure of an amyloid-beta-induced mouse model. Methods: Mice received intranasal Aß1-42 (5 µg/10 µL) exposure once daily for seven consecutive days. Quercetin was orally administered to them at 30 mg kg-1 and 100 mg kg-1 doses for one week starting from day five following Aß1-42 peptide administration. Following this, the animals were evaluated for neurobehavioral parameters using a Morris water maze test and a novel object recognition test. Further to this, the biomarkers for neuroinflammation and neurodegeneration were evaluated in the hippocampus and cortex regions of the brain in these animals. Results: Multiple exposures to intranasal Aß led to a significant decline in the learning and cognitive memory of the animals, whereas oral treatment with quercetin at dosages of 30 and 100 mg kg-1 alleviated Aß-induced effects. Quercetin treatment significantly reduced Aß accumulation, oxidative stress and proinflammatory cytokine biomarkers in the brain. In addition, it also alleviated the activation of astrocytic biomarkers, amyloid precursor protein and phosphorylated-tau proteins in the brain. Conclusion: Quercetin was found to be a potent antioxidant, anti-inflammatory compound with protection against neurodegenerative damage and improved learning and cognitive memory in a repeated Aß-exposure model of AD.

Coadministration of Quercetin and Indocyanine Green via PEGylated Phospholipid Micelles for Augmented Chem-Photothermal Combination Tumor Therapy.

A significant impediment persists in developing multicomponent nanomedicines designed to dismantle the heat shock protein (HSP)-based protective mechanism of malignant tumors during photothermal therapy. Herein, well-defined PEGylated phospholipid micelles were utilized to coencapsulate quercetin (QUE, a natural anticancer agent and potent HSP inhibitor) and indocyanine green (ICG, a photothermal agent) with the aim of achieving synchronized and synergistic drug effects. The subsequent investigations validated that the tailored micellar system effectively enhanced QUE's water solubility and augmented its cellular internalization efficiency. Intriguingly, the compositional PEGylated phospholipids induced extraordinary endoplasmic reticulum stress, thereby sensitizing the tumor cells to QUE. Furthermore, QUE played a crucial role in inhibiting the stress-induced overexpression of HSP70, thereby augmenting the photothermal efficacy of ICG. In systemic applications, the proposed nanotherapeutics exhibited preferential accumulation within tumors and exerted notable tumoricidal effects against 4T1 xenograft tumors under 808 nm near-infrared irradiation, facilitated by prominent near-infrared fluorescence imaging-guided chemo-photothermal therapy. Therefore, our strategy for fabricating multicomponent nanomedicines emerges as a coordinated platform for optimizing antitumor therapeutic efficacy and offers valuable insights for diverse therapeutic modalities.

Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial.

Preclinical evidence demonstrates that senescent cells accumulate with aging and that senolytics delay multiple age-related morbidities, including bone loss. Thus, we conducted a phase 2 randomized controlled trial of intermittent administration of the senolytic combination dasatinib plus quercetin (D + Q) in postmenopausal women (n = 60 participants). The primary endpoint, percentage changes at 20 weeks in the bone resorption marker C-terminal telopeptide of type 1 collagen (CTx), did not differ between groups (median (interquartile range), D + Q -4.1% (-13.2, 2.6), control -7.7% (-20.1, 14.3); P = 0.611). The secondary endpoint, percentage changes in the bone formation marker procollagen type 1 N-terminal propeptide (P1NP), increased significantly (relative to control) in the D + Q group at both 2 weeks (+16%, P = 0.020) and 4 weeks (+16%, P = 0.024), but was not different from control at 20 weeks (-9%, P = 0.149). No serious adverse events were observed. In exploratory analyses, the skeletal response to D + Q was driven principally by women with a high senescent cell burden (highest tertile for T cell p16 (also known as CDKN2A) mRNA levels) in which D + Q concomitantly increased P1NP (+34%, P = 0.035) and reduced CTx (-11%, P = 0.049) at 2 weeks, and increased radius bone mineral density (+2.7%, P = 0.004) at 20 weeks. Thus, intermittent D + Q treatment did not reduce bone resorption in the overall group of postmenopausal women. However, our exploratory analyses indicate that further studies are needed testing the hypothesis that the underlying senescent cell burden may dictate the clinical response to senolytics. ClinicalTrials.gov identifier: NCT04313634 .

Optimization of atorvastatin and quercetin-loaded solid lipid nanoparticles using Box-Behnken design.

Aim: The study explores the synergistic potential of atorvastatin (ATR) and quercetin (QUER)- loaded solid lipid nanoparticles (SLN) in combating breast cancer. Materials & methods: SLNs were synthesized using a high-shear homogenization method and optimized using Box-Behnken design. The SLNs were characterized and evaluated for their in vitro anticancer activity. Results: The optimized SLN exhibited narrow size distribution (PDI = 0.338 ± 0.034), a particle size of 72.5 ± 6.5 nm, higher entrapment efficiency (<90%), sustained release and spherical surface particles. The in vitro cytotoxicity studies showed a significant reduction in IC50 values on MDA-MB-231 cell lines. Conclusion: We report a novel strategy of repurposing well-known drugs and encapsulating them into SLNs as a promising drug-delivery system against breast cancer.

[Box: see text].

Liposomal quercetin: A promising strategy to combat hepatic insulin resistance and inflammation in type 2 diabetes mellitus.

In type 2 diabetes mellitus, hepatic insulin resistance is intricately associated with oxidative stress and inflammation. Nonetheless, the lack of therapeutic interventions directly targeting hepatic dysfunction represents a notable gap in current treatment options. Flavonoids have been explored due to their potential antidiabetic effects. However, these compounds are associated with low bioavailability and high metabolization. In the present study, four flavonoids, kaempferol, quercetin, kaempferol-7-O-glucoside and quercetin-7-O-glucoside, were studied in a cellular model of hepatic insulin resistance using HepG2 cells. Quercetin was selected as the most promising flavonoid and incorporated into liposomes to enhance its therapeutic effect. Quercetin liposomes had a mean size of 0.12 µm, with an incorporation efficiency of 93 %. Quercetin liposomes exhibited increased efficacy in modulating insulin resistance. This was achieved through the modulation of Akt expression and the attenuation of inflammation, particularly via the NF-κB pathway, as well as the regulation of PGE2 and COX-2 expression. Furthermore, quercetin liposomes displayed a significant advantage over free quercetin in attenuating the production of reactive pro-oxidant species. These findings open new avenues for developing innovative therapeutic strategies to manage diabetes, emphasizing the potential of quercetin liposomes as a promising approach for targeting both hepatic insulin resistance and associated inflammation.

Development of quercetin-loaded electrospun nanofibers through shellac coating on gelatin: Characterization, colon-targeted delivery, and anticancer activity.

Quercetin possesses multiple biological activities. To achieve efficient colon-specific release of quercetin, new composite nanofibers were developed by coating pH-responsive shellac on hydrophilic gelatin through coaxial electrospinning. These composite nanofibers contained bead-like structures. The encapsulation efficiency (87.6-98.5 %) and loading capacity (1.4-4.1 %) varied with increasing the initial quercetin addition amount (2.5-7.5 %). FTIR, XRD, and TGA results showed that the quercetin was successfully encapsulated in composite nanofibers in an amorphous state, with interactions occurring among quercetin, gelatin, and shellac. Composite nanofibers had pH-responsive surface wettability due to the shellac coating. In vitro digestion experiments showed that these composite nanofibers were highly stable in the upper gastrointestinal tract, with quercetin release ranging from 4.75 % to 12.54 %. In vivo organ distribution and pharmacokinetic studies demonstrated that quercetin could be sustainably released in the colon after oral administration of composite nanofibers. Besides, the enhanced anticancer activity of composite nanofibers was confirmed against HCT-116 cells by analyzing their effect on cell viability, cell cycle, and apoptosis. Overall, these novel composite nanofibers could deliver efficiently quercetin to the colon and achieve its sustained release, thus potential to regulate colon health. This system is also helpful in delivering other bioactives to the colon and exerting their functional effects.

[Liposome co-delivery of quercetin and doxorubicin in inhibiting retinoblastoma by regulating epithelial-mesenchymal transition process].

Regulating the process of epithelial-mesenchymal transition(EMT) is an essential strategy to inhibit tumor growth and metastasis. This study is based on the EMT process of retinoblastoma and constructs quercetin(QUE) and doxorubicin(DOX) co-loaded liposome(QD Lipo) to investigate the therapeutic effect and mechanisms of combined QUE and DOX treatment on retinoblastoma. Single-factor experiments were conducted to optimize the prescription process of QD Lipo. Eventually, spherical particles with a diameter of(108.87±1.93) nm, a PDI of 0.13±0.02, and a Zeta potential of(-34.83±1.92) mV were obtained. The encapsulation rates of QUE and DOX were 96.20%±4.40% and 91.17%±4.41%, respectively. Y79 human retinoblastoma cells were used as an in vitro cellular model, and confocal microscopy demonstrated that QD Lipo could enhance Y79 uptake efficiency. The CCK-8 assay confirmed that the optimal combination therapy effect of QUE and DOX occurred at a mass ratio of 1∶1 to 1∶2. Flow cytometry showed that QD Lipo enhanced the induction of apoptosis in Y79 cells. Western blot analysis revealed that QD Lipo significantly reduced the expression of EMT pathway-related proteins vimentin and α-SMA. Fluorescence assays detected a significant decrease in ROS levels in Y79 cells after treatment with QD. These results indicated that liposomal co-delivery of QUE and DOX can enhance drug delivery efficiency to retinoblastoma cells, inhibit the EMT process in retinoblastoma by downregulating ROS levels, and enhance the cytotoxicity of DOX against retinoblastoma.

Quercetin intervention reduced hepatic fat deposition in patients with nonalcoholic fatty liver disease: a randomized, double-blind, placebo-controlled crossover clinical trial.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become a growing public health problem worldwide. However, there is still lack of effective treatment strategies except lifestyle intervention. OBJECTIVES: To evaluate whether quercetin improves intrahepatic lipid content in patients with NAFLD. METHODS: In this randomized, double-blind, placebo-controlled crossover trial, 41 patients with NAFLD were randomly assigned to receive the quercetin (500 mg) or placebo capsules for 12 wk, then switched interventions for another 12 wk after a 4-wk washout period. The primary outcome was intrahepatic lipid content evaluated by magnetic resonance imaging estimated proton density fat fraction. The secondary outcomes were liver function measurements, etc. Safety outcomes included blood routine. RESULTS: A total of 36 patients completed the trial. In intention-to-treat analyses, the quercetin intervention moderately decreased the intrahepatic lipid contents from 11.5% ± 6.4% to 9.6% ± 5.8%, compared with the placebo intervention (decreased by 0.1% ± 2.6%, P = 0.013 and adjusted P value is 0.028). Body weight and body mass index were mildly reduced by 1.5 ± 2.6 kg and 0.5 ± 0.9 kg/m2 after the quercetin intervention (P < 0.05 and both adjusted P values are 0.038), whereas the reductions were only 0.2 ± 1.8 kg and 0.1 ± 0.7 kg/m2 after the placebo intervention. The intrahepatic lipid content reductions were noticeably positively associated with the body weight losses after the quercetin and placebo interventions (r = 0.557 and 0.412, P < 0.001 and P = 0.007, respectively). Subgroup analyses found that the reduction of intrahepatic lipid contents in females (3.0% ± 3.7%) was about twice as large as that in males (1.4% ± 2.5%) with a trend of statistical significance (P = 0.113 and adjusted P value is 0.061). There were no significant differences in other secondary and safety outcomes. No adverse events associated with study intervention were found. CONCLUSIONS: Twelve weeks treatment of quercetin could reduce intrahepatic lipid contents in patients with NAFLD, possibly explained by a slightly larger body weight loss in the quercetin group. TRIAL REGISTRATION: The trial is registered at www.chictr.org.cn as ChiCTR2100047904.

Controlled Quercetin Release by Fluorescent Mesoporous Nanocarriers for Effective Anti-Adipogenesis.

Introduction: Quercetin (QUER), a flavonoid abundant in fruits and vegetables, is emerging as a promising alternative therapeutic agent for obesity treatment due to its antioxidant and anti-adipogenic properties. However, the clinical application of QUER is limited by its poor solubility, low bioavailability, and potential toxicity at high doses. To address these challenges, this study aims to develop an advanced drug delivery system using fluorescent mesoporous silica nanoparticles (FMSNs) coated with polydopamine (PDA) for the efficient and sustained delivery of QUER to inhibit adipogenesis. Methods: The research included the synthesis of PDA-coated FMSNs for encapsulation of QUER, characterization of their mesoporous structures, and systematic investigation of the release behavior of QUER. The DPPH assay was used to evaluate the sustained radical scavenging potential. Concentration-dependent effects on 3T3-L1 cell proliferation, cellular uptake and adipogenesis inhibition were investigated. Results: PDA-coated FMSNs exhibited well-aligned mesoporous structures. The DPPH assay confirmed the sustained radical scavenging potential, with FMSNs-QUER@PDA showing 53.92 ± 3.48% inhibition at 72 h, which was higher than FMSNs-QUER (44.66 ± 0.57%) and free QUER (43.37 ± 5.04%). Concentration-dependent effects on 3T3-L1 cells highlighted the enhanced efficacy of PDA-coated FMSNs for cellular uptake, with a 1.5-fold increase compared to uncoated FMSNs. Adipogenesis inhibition was also improved, with relative lipid accumulation of 44.6 ± 4.6%, 37.3 ± 4.6%, and 36.5 ± 7.3% at 2.5, 5, and 10 µM QUER concentrations, respectively. Conclusion: The study successfully developed a tailored drug delivery system, emphasizing sustained QUER release and enhanced therapeutic effects. FMSNs, especially when coated with PDA, exhibit promising properties for efficient QUER delivery, providing a comprehensive approach that integrates advanced drug delivery technology and therapeutic efficacy.

Surface modified niosomal quercetin with cationic lipid: an appropriate drug delivery system against Pseudomonas aeruginosa Infections.

The Increase in infections caused by resistant strains of Pseudomonas aeruginosa poses a formidable challenge to global healthcare systems. P. aeruginosa is capable of causing severe human infections across diverse anatomical sites, presenting considerable therapeutic obstacles due to its heightened drug resistance. Niosomal drug delivery systems offer enhanced pharmaceutical potential for loaded contents due to their desirable properties, mainly providing a controlled-release profile. This study aimed to formulate an optimized niosomal drug delivery system incorporating stearylamine (SA) to augment the anti-bacterial and anti-biofilm activities of quercetin (QCT) against both standard and clinical strains of P. aeruginosa. QCT-loaded niosome (QCT-niosome) and QCT-loaded SA- niosome (QCT-SA- niosome) were synthesized by the thin-film hydration technique, and their physicochemical characteristics were evaluated by field emission scanning electron microscopy (FE-SEM), zeta potential measurement, entrapment efficacy (EE%), and in vitro release profile. The anti-P. aeruginosa activity of synthesized niosomes was assessed using minimum inhibitory and bactericidal concentrations (MICs/MBCs) and compared with free QCT. Additionally, the minimum biofilm inhibitory and eradication concentrations (MBICs/MBECs) were carried out to analyze the ability of QCT-niosome and QCT-SA-niosome against P. aeruginosa biofilms. Furthermore, the cytotoxicity assay was conducted on the L929 mouse fibroblasts cell line to evaluate the biocompatibility of the formulated niosomes. FE-SEM analysis revealed that both synthesized niosomal formulations exhibited spherical morphology with different sizes (57.4 nm for QCT-niosome and 178.9 nm for QCT-SA-niosome). The EE% for cationic and standard niosomal formulations was reported at 75.9% and 59.6%, respectively. Both formulations showed an in vitro sustained-release profile, and QCT-SA-niosome exhibited greater stability during a 4-month storage time compared to QCT-niosome. Microbial experiments indicated that both prepared formulations had higher anti-bacterial and anti-biofilm activities than free QCT. Also, the QCT-SA-niosome exhibited greater reductions in MIC, MBC, MBIC, and MBEC values compared to the QCT-niosome at equivalent concentrations. This study supports the potential of QCT-niosome and QCT-SA-niosome as effective agents against P. aeruginosa infections, manifesting significant anti-bacterial and anti-biofilm efficacy alongside biocompatibility with L929 cell lines. Furthermore, our results suggest that optimized QCT-niosome with cationic lipids could efficiently target P. aeruginosa cells with negligible cytotoxic effect.

Pharmacokinetics of Dihydroquercetin after Single and Repeated Administration to Rats.

The pharmacokinetic properties of dihydroquercetin (DHQ) were studied after single and repeated (for 3 days) administration to rats in the form of a starch suspension at a dose of 25 mg/kg. Blood samples were collected using a permanent catheter in the jugular vein in 2, 5, 10, 20, and 30 min and in 1, 2, 4, and 6 h after administration. Before the repeated administration (5 min), blood sample was collected to assess the concentration of DHQ at the zero time point. Quantitative analysis was carried out by HPLC-tandem mass spectrometry. DHQ was very quickly absorbed by the gastrointestinal tract and quickly eliminated from the body. Repeated administration of DHQ did not lead to its accumulation in the body but had an effect on the enzymatic system with a subsequent increase in DHQ exposure (accumulation factor >1 by AUC after repeated administration).

Dietary supplementation with quercetin: an ideal approach for improving meat quality and oxidative stability of broiler chickens.

This study aimed to improve the eating quality of yellow-feathered broiler chicks by feeding them corn-soybean meal diets supplemented with 250, 500, and 1,000 mg/kg quercetin. we examined the impact of varying doses of dietary quercetin on the sensory quality of chicken breast meat as well as on the antioxidant enzymes, antioxidant-related signaling molecules, structure and thermal stability of myofibrillar protein (MPs), and microstructure of myogenic fibers in the meat during 24 h of postslaughter aging. Additionally, we investigated the potential correlations among antioxidant capacity, MP structure, and meat quality parameters. The results indicated that dietary supplementations with 500 and 1,000 mg/kg quercetin improved the physicochemical properties and eating quality of yellow-feathered broiler chicken breast meat during 12 to 24 h postslaughter. Additionally, quercetin improved the postslaughter oxidative stress status and reduced protein and lipid oxidation levels. It also increased hydrogen bonding interactions and α-helix content during 6 to 12 h postslaughter and decreased ß-sheet content during 12 to 24 h postslaughter in chicken breast MP. This resulted in improved postslaughter MP structure and thermal stability. The correlation results indicated that the enhancement of antioxidant capacity and MP structure enhanced the physicochemical and edible qualities of yellow-feathered broiler chicken breast meat. In conclusion, the current findings suggest that dietary supplementation with quercetin is an ideal approach for improving the eating quality of chicken meat, thereby broadening our understanding of theoretical and technological applications for improving the quality of chicken.

Synergistic effects of quercetin-loaded CoFe2O4@Liposomes regulate DNA damage and apoptosis in MCF-7 cancer cells: based on biophysical magnetic hyperthermia.

INTRODUCTION: Breast cancer (BC) is the most common malignancy in women globally. Significant progress has been made in developing structural nanoparticles (NPs) and formulations for targeted smart drug delivery (SDD) of pharmaceuticals, improving the precision of tumor cell targeting in therapy. SIGNIFICANCE: Magnetic hyperthermia (MHT) treatment using magneto-liposomes (MLs) has emerged as a promising adjuvant cancer therapy. METHODS: CoFe2O4 magnetic NPs (MNPs) were conjugated with nanoliposomes to form MLs, and the anticancer drug quercetin (Que) was loaded into MLs, forming Que-MLs composites for antitumor approach. The aim was to prepare Que-MLs for DD systems (DDS) under an alternating magnetic field (AMF), termed chemotherapy/hyperthermia (chemo-HT) techniques. The encapsulation efficiency (EE), drug loading capacity (DL), and drug release (DR) of Que and Que-MLs were evaluated. RESULTS: The results confirmed successful Que-loading on the surface of MLs, with an average diameter of 38 nm and efficient encapsulation into MLs (69%). In vitro, experimental results on MCF-7 breast cells using MHT showed high cytotoxic effects of novel Que-MLs on MCF-7 cells. Various analyses, including cytotoxicity, apoptosis, cell migration, western blotting, fluorescence imaging, and cell membrane internalization, were conducted. The Acridine Orange-ethidium bromide double fluorescence test identified 35% early and 55% late apoptosis resulting from Que-MLs under the chemo-HT group. TEM results indicated MCF-7 cell membrane internalization and digestion of Que-MLs, suggesting the presence of early endosome-like vesicles on the cytoplasmic periphery. CONCLUSIONS: Que-MLs exhibited multi-modal chemo-HT effects, displaying high toxicity against MCF-7 BC cells and showing promise as a potent cytotoxic agent for BC chemotherapy.